Generic homonyms in the Colydiinae (Coleoptera: Zopheridae)

New replacement names are proposed: Megapnosaurus Ivie, Slipinski and Wegrzynowicz NEW REPLACEMENT NAME for Syntarsus Raath 1969 (Ceratosauria: Coelophysidae), not Syntarsus Fairmaire 1869 (Coleoptera: Zopheridae: Colydiinae); and Stephaniolus Ivie, Slipinski and Wegrzynowicz NEW REPLACEMENT NAME for Pseudotaphrus Stephan 1989 (Coleoptera: Zopheridae: Colydiinae) not Pseudotaphrus Cossmann 1888 (Mollusca: Rissoiidae). These result in the new combinations Megapnosaurus rhodesiensis (Raath 1961) NEW COMBINATION, Megapnosaurus kayentalwtae (Rowe 1989) NEW COMBINATION and Stephanioh£s longus (Stephan 1989) NEW COMBINATION

New records and synonyms in the Colydiinae and Pycnomerini (Coleoptera: Zopheridae)

New synonyms are proposed for: Pethelispa arizonica Dajoz 1992 = Pycnomerus arizonicus Stephan 1989 NEW SYNONYMY; Microprius cubanus Slipinski 1985 = Eudesmula california Dajoz 1992 = Microprius rufulus (Motschulsky 1863) NEW SYNONYMIES; andAulonium chilense Dajoz 1980=Aulonium parallelopedium (Say 1826) NEW SYNONYMY. Colobicus parilis Pascoe is recorded from Louisiana, a new distributional record for the New World

Role of astrocytes in manganese mediated neurotoxicity

Astrocytes are responsible for numerous aspects of metabolic support, nutrition, control of the ion and neurotransmitter environment in central nervous system (CNS). Failure by astrocytes to support essential neuronal metabolic requirements plays a fundamental role in the pathogenesis of brain injury and the ensuing neuronal death. Astrocyte-neuron interactions play a central role in brain homeostasis, in particular via neurotransmitter recycling functions. Disruption of the glutamine (Gln)/glutamate (Glu) -γ-aminobutyric acid (GABA) cycle (GGC) between astrocytes and neurons contributes to changes in Glu-ergic and/or GABA-ergic transmission, and is associated with several neuropathological conditions, including manganese (Mn) toxicity. In this review, we discuss recent advances in support of the important roles for astrocytes in normal as well as neuropathological conditions primarily those caused by exposure to Mn

Astrocytes in mouse models of tauopathies acquire early deficits and lose neurosupportive functions

Microtubule-associated protein tau aggregates constitute the characteristic neuropathological features of several neurodegenerative diseases grouped under them name of tauopathies. It is now clear that the process of tau aggregation is associated with neurodegeneration. Several transgenic tau mouse models have been developed where tau progressively aggregates, causing neuronal death. Previously we have shown that transplantation of astrocytes in P301S tau transgenic mice rescues cortical neuron death, implying that the endogenous astrocytes are deficient in survival support. We now show that the gliosis markers GFAP and S100β are elevated in brains from P301S tau mice compared to control C57Bl/6 mice whereas the expression of proteins involved in glutamine/glutamate metabolism are reduced, pointing to a functional deficit. To test whether astrocytes from P301S mice are intrinsically deficient, we co-cultured astrocytes and neurons from control and P301S mice. Significantly more C57-derived and P301S-derived neurons survived when cells were cultured with C57-derived astrocytes or astrocyte conditioned medium (C57ACM) than with P301S derived astrocytes or P301SACM, or ACM from P301L tau mice, where the transgene is also specifically expressed in neurons. The astrocytic alterations developed in mice during the first postnatal week of life. In addition, P301SACM significantly decreased presynaptic (synaptophysin, SNP) and postsynaptic (PSD95) protein expression in cortical neuron cultures whereas C57-ACM enhanced these markers. Since thrombospondin 1 (TSP-1) is a major survival and synaptogenic factor, we examined whether TSP-1 is deficient in P301S mouse brains and ACM. Significantly less TSP-1 was expressed in the brains of P301S tau mice or produced by P301S-derived astrocytes, whereas supplementation of P301SACM with TSP-1 increased its neurosupportive capacity. Our results demonstrate that P301S-derived astrocytes acquire an early functional deficiency that may explain in part the loss of cortical neurons in the P301S tau mice.The study was supported by Alzheimer’s Research UK with ARUK project grant RG62844 to MGS and ARUK extension grant RG80005 to MGS and MSW. We also acknowledge a contribution from the NC3Rs (Grant NC/L000741/1 to MGS and AMT)

Depopulation of dense α-synuclein aggregates is associated with rescue of dopamine neuron dysfunction and death in a new Parkinson's disease model.

Parkinson's disease (PD) is characterized by the presence of α-synuclein aggregates known as Lewy bodies and Lewy neurites, whose formation is linked to disease development. The causal relation between α-synuclein aggregates and PD is not well understood. We generated a new transgenic mouse line (MI2) expressing human, aggregation-prone truncated 1-120 α-synuclein under the control of the tyrosine hydroxylase promoter. MI2 mice exhibit progressive aggregation of α-synuclein in dopaminergic neurons of the substantia nigra pars compacta and their striatal terminals. This is associated with a progressive reduction of striatal dopamine release, reduced striatal innervation and significant nigral dopaminergic nerve cell death starting from 6 and 12 months of age, respectively. In the MI2 mice, alterations in gait impairment can be detected by the DigiGait test from 9 months of age, while gross motor deficit was detected by rotarod test at 20 months of age when 50% of dopaminergic neurons in the substantia nigra pars compacta are lost. These changes were associated with an increase in the number and density of 20-500 nm α-synuclein species as shown by dSTORM. Treatment with the oligomer modulator anle138b, from 9 to 12 months of age, restored striatal dopamine release, prevented dopaminergic cell death and gait impairment. These effects were associated with a reduction of the inner density of large α-synuclein aggregates and an increase in dispersed small α-synuclein species as revealed by dSTORM. The MI2 mouse model recapitulates the progressive dopaminergic deficit observed in PD, showing that early synaptic dysfunction is associated to fine behavioral motor alterations, precedes dopaminergic axonal loss and neuronal death that become associated with a more consistent motor deficit upon reaching a certain threshold. Our data also provide new mechanistic insight for the effect of anle138b's function in vivo supporting that targeting α-synuclein aggregation is a promising therapeutic approach for PD

L444P Gba1 mutation increases formation and spread of α-synuclein deposits in mice injected with mouse α-synuclein pre-formed fibrils

Parkinson disease is the most common neurodegenerative movement disorder, estimated to affect one in twenty-five individuals over the age of 80. Mutations in glucocerebrosidase 1 (GBA1) represent the most common genetic risk factor for Parkinson disease. The link between GBA1 mutations and α-synuclein accumulation, a hallmark of Parkinson disease, is not fully understood. Following our recent finding that Gba1 mutations lead to increased α-synuclein accumulation in mice, we have studied the effects of a single injection of mouse α-synuclein pre-formed fibrils into the striatum of Gba1 mice that carry a L444P knock-in mutation. We found significantly greater formation and spread of α-synuclein inclusions in Gba1-transgenic mice compared to wild-type controls. This indicates that the Gba1 L444P mutation accelerates α-synuclein pathology and spread

L444P Gba1 mutation increases formation and spread of α-synuclein deposits in mice injected with mouse α-synuclein pre-formed fibrils.

Parkinson disease is the most common neurodegenerative movement disorder, estimated to affect one in twenty-five individuals over the age of 80. Mutations in glucocerebrosidase 1 (GBA1) represent the most common genetic risk factor for Parkinson disease. The link between GBA1 mutations and α-synuclein accumulation, a hallmark of Parkinson disease, is not fully understood. Following our recent finding that Gba1 mutations lead to increased α-synuclein accumulation in mice, we have studied the effects of a single injection of mouse α-synuclein pre-formed fibrils into the striatum of Gba1 mice that carry a L444P knock-in mutation. We found significantly greater formation and spread of α-synuclein inclusions in Gba1-transgenic mice compared to wild-type controls. This indicates that the Gba1 L444P mutation accelerates α-synuclein pathology and spread

CSP alpha reduces aggregates and rescues striatal dopamine release in alpha-synuclein transgenic mice

alpha-Synuclein aggregation at the synapse is an early event in Parkinson's disease and is associated with impaired striatal synaptic function and dopaminergic neuronal death. The cysteine string protein (CSP alpha) and alpha-synuclein have partially overlapping roles in maintaining synaptic function and mutations in each cause neurodegenerative diseases. CSP alpha is a member of the DNAJ/HSP40 family of co-chaperones and like alpha-synuclein, chaperones the SNARE complex assembly and controls neurotransmitter release. alpha-Synuclein can rescue neurodegeneration in CSP alpha KO mice. However, whether alpha-synuclein aggregation alters CSP alpha expression and function is unknown. Here we show that alpha-synuclein aggregation at the synapse is associated with a decrease in synaptic CSP alpha and a reduction in the complexes that CSP alpha forms with HSC70 and STG alpha. We further show that viral delivery of CSP alpha rescues in uitro the impaired vesicle recycling in PC12 cells with alpha-synuclein aggregates and in uiuo reduces synaptic alpha-synuclein aggregates increasing monomeric alpha-synuclein and restoring normal dopamine release in 1-120h alpha Syn mice. These novel findings reveal a mechanism by which alpha-synuclein aggregation alters CSP alpha at the synapse, and show that CSP alpha rescues alpha-synuclein aggregation-related phenotype in 1-120h alpha Syn mice similar to the effect of alpha-synuclein in CSP alpha KO mice. These results implicate CSP alpha as a potential therapeutic target for the treatment of earlystage Parkinson's disease

Effects of Post-Translational Modifications of Fibrinogen on Clot Formation, Clot Structure, and Fibrinolysis: A Systematic Review

OBJECTIVE: Post-translational modifications of fibrinogen influence the occurrence and progression of thrombotic diseases. In this systematic review, we assessed the current literature on post-translational modifications of fibrinogen and their effects on fibrin formation and clot characteristics. Approach and Results: A systematic search of Medline, Embase, Cochrane Library, and Web of Science was performed to find studies reporting post-translational modifications of fibrinogen and the effects on clot formation and structure. Both in vitro studies and ex vivo studies using patient material were included. One hundred five articles were included, describing 11 different modifications of fibrinogen. For the best known and studied modifications, conclusions could be drawn about their effect on clot formation and structure. Oxidation, high levels of nitration, and glycosylation inhibit the rate of polymerization, resulting in dense clots with thinner fibers, while low levels of nitration increase the rate of polymerization. Glycation showed different results for polymerization, but f

The L444P Gba1 mutation enhances alpha-synuclein induced loss of nigral dopaminergic neurons in mice

Mutations in glucocerebrosidase 1 (GBA1) represent the most prevalent risk factor for Parkinson's disease. The molecular mechanisms underlying the link between GBA1 mutations and Parkinson's disease are incompletely understood. We analysed two aged (24-month-old) Gba1 mouse models, one carrying a knock-out mutation and the other a L444P knock-in mutation. A significant reduction of glucocerebrosidase activity was associated with increased total alpha-synuclein accumulation in both these models. Gba1 mutations alone did not alter the number of nigral dopaminergic neurons nor striatal dopamine levels. We then investigated the effect of overexpression of human alpha-synuclein in the substantia nigra of aged (18 to 21-month-old) L444P Gba1 mice. Following intraparenchymal injections of human alpha-synuclein carrying viral vectors, pathological accumulation of phosphorylated alpha-synuclein occurred within the transduced neurons. Stereological counts of nigral dopaminergic neurons revealed a significantly greater cell loss in Gba1-mutant than wild-type mice. These results indicate that Gba1 deficiency enhances neuronal vulnerability to neurodegenerative processes triggered by increased alpha-synuclein expression